LECTURE 3 (Lupus)

Question 1

What is Systemic Lupus Erythematosus (SLE)?

Answer 1

An autoimmune disease mostly affecting women, especially African-Americans, developing between 15-45

IMMUNOLOGY:
Antibodies form against nuclear material in cells [key finding: anti-nuclear antibodies (ANA) in plasma] -> once ANA form, they form antibody-antigen complexes that circulate in plasma (Type III hypersensitivity reaction) -> deposits in many different tissues causing different symptoms -> activation of complement cascade cause damage [key finding: low C3/C4 levels (hypocomplementemia) + low CH50 levels]

CAUSES:
- unknown
- genetic, immune, environmental factors + viruses and UV light may play a role

Question 2

Which antibodies cause Lupus?

Answer 2

• Anti-nuclear antibodies (ANA)
• Anti-double stranded DNA (anti-dsDNA)
• Anti-smith (anti-Sm)

Question 3

What are Anti-nuclear antibodies (ANA)?

Answer 3

A type of antibody present in the serum of lupus patients and many other autoimmune disorders (also present in 5% of normal patients)

• Sensitive but not a specific test -> Negative test = disease is very unlikely

Question 4

What are Anti-double stranded DNA (anti-dsDNA) antibodies?

Answer 4

Antibodies specific for Lupus and is associated with disease activity (increase during flare-ups) and renal involvement (more anti-dsDNA increases risk of glomerulonephritis)

Question 5

What are Anti-smith (anti-Sm) antibodies?

Answer 5

Antibodies specific for Lupus that are directed against small nuclear ribonucleoproteins (snRNPs)

Question 6

What are small nuclear ribonucleic proteins (snRNPs)?

Answer 6

• Combine with RNA transcripts forming a “spliceosome” -> removes a portion of the RNA transcript “splicing” to translate into a protein
• Antibodies against snRNPs found in lupus (anti-Sm)

Question 7

Anti-smith antibodies is part of a panel of blood tests against nuclear antigens called the ______ panel

Answer 7

ENA panel

(Extractable Nuclear Antigens)

Question 8

What is the function of Extractable Nuclear Antigens?

Answer 8

A panel of blood tests sent for patients who have suspected autoimmune disorders

Question 9

What are the symptoms of Lupus?

Answer 9

• Signs of inflammation: Fever, weight loss, fatigue, lymphadenopathy
• Malar “butterfly” rash
• “Discoid” lesion (circular skin lesion usually on forearm)
• Raynaud’s phenomenon
• Oral/nasal ulcers
• Arthritis (tender, swollen joints)
• Serositis = inflammation of pleura (pain with inspiration), inflammation of pericardium (pericarditis)
• Anemia, thrombocytopenia, leukopenia due to Antibody attack of cells (TYPE II HYPERSENSITIVITY)
• Lupus Cerebritis
• Lupus Nephropathy
• Libman-Sacks (marantic) endocarditis

[symptoms are not constant - FLARES and remissions for a period of time]

Question 10

Describe the Malar “butterfly” rash

Answer 10

• A classic lupus skin finding
• Common on sunlight exposure

Question 10

Describe Raynaud’s phenomenon

Answer 10

A result of vasospasm of arteries supplying blood to the fingertips resulting in ischaemia

SYMPTOMS:
- White/blue fingertips
- Painful on exposure to the cold
- Fingertip ulcers

It can also be seen in other conditions either by itself or secondary to other autoimmune disorders

Question 10

What is Lupus Cerebritis?

Answer 10

When lupus affects the brain and spinal cord

SYMPTOMS:
- Cognitive dysfunction (confusion and memory loss during flares)
- Stroke
- Seizures

Question 11

What is Lupus Nephropathy?

Answer 11

When lupus affects the kidneys and can present as the nephritic or nephrotic syndrome (or both) and is the common cause of death in lupus

• Nephritic = most common SLE renal syndrome
• Nephrotic = not as common

[Nephritic syndrome = when inflamed glomeruli do not properly filter RBCs, Nephrotic syndrome = when glomeruli do not properly filter albumin]

Question 12

What is Libman-Sacks/Marantic endocarditis?

Answer 12

A rare form of endocarditis that occurs in Lupus patients.

• Non-bacterial
• Due to inflammation of valves as a result of lupus
• Classically affects both sides of the mitral valve

Question 13

What are Anti-phospholipid antibodies?

Answer 13

Antibodies against proteins in phospholipids that can occur in association with lupus (can also occur as a primary problem without having lupus)

CLINICAL CONSEQUENCES:
- “Antiphospholipid syndrome” (develop antiphospholipid antibodies that cause development of venous/arterial thrombosis -> DVT, stroke, foetal loss)
- Increased PTT
- False positive syphilis test

Question 14

What are the three clinically relevant anti-phospholipid antibodies?

Answer 14

• Anti-cardiolipin
  [antibody responsible for false positive syphilis (RPR/VDRL) test since also bind with RPR/VDRL antigens]
• Lupus anticoagulant
  [intereferes with PTT test by giving a false elevation]
• Anti-B2 glycoprotein

Question 15

How do you diagnose lupus?

Answer 15

You need to diagnose 4 out of 11 criteria

CRITERIA:
1. Malar rash
2. Discoid rash
3. Photosensitivity
4. Oral ulcers
5. Arthritis
6. Serositis
7. Cerebritis/CNS involvement
8. Renal disease
9. “Penias”
10. ANA
11. Another antibody test = Anti-dsDNA or Anti-Sm or anti-phospholipid

Question 16

What is Drug-induced lupus?

Answer 16

Lupus-like syndrome after taking a drug

CLASSIC DRUGS:
- Isoniazid/INH (Tuberculosis drug)
- Hydralazine (Blood pressure drug)
- Procainamide (Anti-arythmic)

SYMPTOMS:
- Rash
- Arthritis
- Penias
- Positive ANA
COMPLICATIONS:
- Kidney or CNS involvement

KEY FEATURES:
- Anti-histone antibodies (rarely elevated in traditional lupus but elevated in drug-induced lupus)
- Resolves on stopping the drug

Question 17

How is Lupus treated?

Answer 17

• Steroids
• Other immunosuppressants
• Avoid sunlight (many are photosensitive + can develop “Malar rash” and flares)
• Causes of death (Renal failure, Infection [many patients take immunosuppressant drugs], Coronary disease

Question 18

What is Neonatal Lupus?

Answer 18

An autoimmune disease in which passive transfer of autoantibodies across the placenta from the mother to the fetus results in fetal and neonatal disease

• Occurs in 1-2% of babies born if mum has autoimmune disease
• Can occur in SLE and Sjögren’s syndrome
• +SSA/Ro or +SSA/La antibodies lead to condition in foetus (elevated in SLE and Sjögren’s syndrome)

SYMPTOMS: (present at birth/first few weeks of life)
- Rash (multiple red, circular lesions on face/scalp)
- Congenital complete heart block (Slow heart rate (around 50s) and does not improve with steroids -> need a pacemaker for the rest of their lives)